CDC7 (cell division cycle 7) is a serine-threonline kinase that plays a critical role in DNA synthesis and is required for the activation of DNA replication origins throughout the S phase of the cell cycle. Inhibition of CDC7 in cancer causes lethal S phase and M phase progression, whereas normal cells survive, mostly likely through induction of cell cycle arrest at the DNA replication checkpoint. It has been reported in the literature that CDC7 is over expressed in many cancers, including triple-negative breast cancer, which is a still highly unmet medical need.1,2,3,4,5.
Among many small molecule CDC 7 inhibitors in the discovery stage and early clinic stage, Exelixis and Takeda separately patented a class of molecules that contains a [5,6]cyclic-4(3H)-pyrimidinone core structure.6,7,8.